Jose Leis, MD, PhD

Jose Leis, MD, PhD, of the Mayo Clinic in Arizona, commented on the promise of checkpoint inhibitors in Richter transformation. “At Mayo, we have treated more than 30 patients with programmed cell death protein 1 (PD-1) blockade. We do see that chronic lymphocytic leukemia (CLL) has low expression of PD-1, and therefore I don’t think we will see good responses to checkpoint inhibition.”

Dr. Leis told The ASCO Post: “In Richter’s, however, we see increased PD-1 expression, so that may be different. I think both nivolumab ­[Opdivo] and pembrolizumab [Keytruda] are producing responses in that group of patients and in combination with Bruton’s tyrosine kinase inhibitors are showing great promise.”

Cautious Optimism

Acalabrutinib is another Bruton’s tyrosine kinase inhibitor with less toxicity, and it may be better, but let’s not jump to conclusions.

— Kanti R. Rai, MD

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Kanti R. Rai, MD, Professor of Medicine, Hofstra Northwell School of Medicine, New Hyde Park, New York, commented on the results of acalabrutinib in Richter transformation, both during the discussion period at the American Society of Hematology (ASH) Annual Meeting & Exposition and for The ASCO Post.

Dr. Rai said the response rates to acalabrutinib were “very encouraging,” but he lamented, “I wish I could feel a Eureka moment.” Dr. Rai asked the speaker whether, in his opinion, new Bruton’s tyrosine kinase inhibitors represent “real hope” in this ­malignancy.

Dr. Hillmen maintained that in a study population “that had failed our best chemoimmunotherapies,” the attainment of single-agent responses “is impressive.” He also acknowledged that single-agent therapy will likely not be effective in this challenging subset. “Single-agent treatment with acalabrutinib or other agents will not be the final answer, but seeing single-agent activity is encouraging as we move toward logical combinations,” he said. “We are making progress, but we certainly have not arrived at the destination.”

Following up with The ASCO Post, Dr. Rai further commented: “I do not intend to cast doubt on these findings, but at the same time showing an early response should not give false hope that a wonderful thing has happened. We are still in a dismal situation with respect to Richter transformation. For decades, we have recognized that it’s essentially a death sentence,” he stated.

Acalabrutinib, Dr. Rai concluded, is “another Bruton’s tyrosine kinase inhibitor with less toxicity, and it may be better, but let’s not jump to ­conclusions.” ■

Disclosure: Dr. Leis reported no potential conflicts of interest. Dr. Rai is on the medical advisory board of Pharmacyclics, Gilead, Incyte, and Roche/Genentech.